View source for Sequence assembly

<p><span style="font-size: small"><span style="color: #000000">In bioinformatics, <b>sequence assembly</b> refers to aligning and merging fragments of a much longer DNA sequence in order to reconstruct the original sequence. This is needed as DNA sequencing technology cannot read whole genomes in one go, but rather small pieces between 20 and 1000 bases, depending on the technology used. Typically the short fragments, called reads, result from shotgun sequencing genomic DNA, or gene transcript (ESTs).</span></span></p>
<p><span style="font-size: small"><span style="color: #000000">The problem of sequence assembly can be compared to taking many copies of a book, passing them all through a shredder, and piecing a copy of the book back together from only shredded pieces. The book may have many repeated paragraphs, and some shreds may be modified to have typos. Excerpts from another book may be added in, and some shreds may be completely unrecognizable.</span></span></p>
<p>&nbsp;</p>
<h2><span style="color: #000000"><span id="Genome_assemblers" class="mw-headline">Genome assemblers</span></span></h2>
<p><span style="font-size: small"><span style="color: #000000">The first sequence assemblers began to appear in the late 1980s and early 1990s as variants of simpler sequence alignment programs to piece together vast quantities of fragments generated by automated sequencing instruments called DNA sequencers. As the sequenced organisms grew in size and complexity (from small viruses over plasmids to bacteria and finally eukaryotes), the assembly programs needed to increasingly employ more and more sophisticated strategies to handle:</span></span></p>
<ul>
    <li><span style="font-size: small"><span style="color: #000000">terabytes of sequencing data which need processing on computing clusters;</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">identical and nearly identical sequences (known as <i>repeats</i>) which can, in the worst case, increase the time and space complexity of algorithms exponentially;</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">and errors in the fragments from the sequencing instruments, which can confound assembly.</span> </span></li>
</ul>
<p><span style="font-size: small"><span style="color: #000000">Faced with the challenge of assembling the first larger eukaryotic genomes, the fruit fly Drosophila melanogaster, in 2000 and the human genome just a year later, scientists developed assemblers like Celera Assembler<sup id="cite_ref-0" class="reference">[1]</sup> and Arachne<sup id="cite_ref-1" class="reference">[2]</sup> able to handle genomes of 100-300 million base pairs. Subsequent to these efforts, several other groups, mostly at the major genome sequencing centers, built large-scale assemblers, and an open source effort known as AMOS<sup id="cite_ref-2" class="reference">[3]</sup> was launched to bring together all the innovations in genome assembly technology under the open source framework.</span></span></p>
<h2><span style="font-size: medium"><span style="color: #000000"><span id="EST_assemblers" class="mw-headline">EST assemblers</span></span></span></h2>
<p><span style="font-size: small"><span style="color: #000000">EST assembly differs from genome assembly in several ways. The sequences for EST assembly are the transcribed mRNA of a cell and represent only a subset of the whole genome. At a first glance, underlying algorithmical problems differ between genome and EST assembly. For instance, genomes often have large amounts of repetitive sequences, mainly in the inter-genic parts. Since ESTs represent gene transcripts, they will not contain these repeats. On the other hand, cells tend to have a certain number of genes that are constantly expressed in very high amounts (housekeeping genes), which again leads to the problem of similar sequences present in high amounts in the data set to be assembled.</span></span></p>
<p><span style="font-size: small"><span style="color: #000000">Furthermore, genes sometimes overlap in the genome (sense-antisense transcription), and should ideally still be assembled separately. EST assembly is also complicated by features like (cis-) alternative splicing, trans-splicing, single-nucleotide polymorphism, recoding, and post-transcriptional modification.</span></span></p>
<h2><span style="font-size: small"><span style="color: #000000"><span id="De-novo_vs._mapping_assembly" class="mw-headline">De-novo vs. mapping assembly</span></span></span></h2>
<p><span style="font-size: small"><span style="color: #000000">In sequence assembly, two different types can be distinguished:</span></span></p>
<ol>
    <li><span style="font-size: small"><span style="color: #000000">de-novo: assembling reads together so that they form a new, previously unknown sequence</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">mapping: assembling reads against an existing backbone sequence, building a sequence that is similar but not necessarily identical to the backbone sequence</span> </span></li>
</ol>
<p><span style="font-size: small"><span style="color: #000000">In terms of complexity and time requirements, de-novo assemblies are orders of magnitude slower and more memory intensive than mapping assemblies. This is mostly due to the fact that the assembly algorithm need to compare every read with every other read (an operation that is has a complexity of O(<var>n</var><sup>2</sup>) but can be reduced to O(<var>n</var> log(<var>n</var>)). Referring to the comparison drawn to shredded books in the introduction: while for mapping assemblies one would have a very similar book as template (perhaps with the names of the main characters and a few locations changed), the de-novo assemblies are more hardcore in a sense as one would not know beforehand whether this would become a science book, or a novel, or a catalogue etc.</span></span></p>
<h2><span style="font-size: small"><span style="color: #000000"><span id="Influence_of_technological_changes" class="mw-headline">Influence of technological changes</span></span></span></h2>
<p><span style="font-size: small"><span style="color: #000000">The complexity of sequence assembly is driven by two major factors: the number of fragments and their lengths. While more and longer fragments allow better identification of sequence overlaps, they also pose problems as the underlying algorithms show quadratic or even exponential complexity behaviour to both number of fragments and their length. And while shorter sequences are faster to align, they also complicate the layout phase of an assembly as shorter reads are more difficult to use with repeats or near identical repeats.</span></span></p>
<p><span style="font-size: small"><span style="color: #000000">In the earliest days of DNA sequencing, scientists could only gain a few sequences of short length (some dozen bases) after weeks of work in laboratories. Hence, these sequences could be aligned in a few minutes by hand.</span></span></p>
<p><span style="font-size: small"><span style="color: #000000">In 1975, the Dideoxy termination method (also known as <i>Sanger sequencing</i>) was invented and until shortly after 2000, the technology was improved up to a point were fully automated machines could churn out sequences in a highly parallelised mode 24 hours a day. Large genome centers around the world housed complete farms of these sequencing machines, which in turn led to the necessity of assemblers to be optimised for sequences from whole-genome shotgun sequencing projects where the reads</span></span></p>
<ul>
    <li><span style="font-size: small"><span style="color: #000000">are about 800&ndash;900 bases long</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">contain sequencing artifacts like sequencing and cloning vectors</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">have error rates between 0.5 and 10%</span> </span></li>
</ul>
<p><span style="font-size: small"><span style="color: #000000">With the Sanger technology, bacterial projects with 20,000 to 200,000 reads could easily be assembled on one computer. Larger ones like the human genome with approximately 35 million reads needed already large computing farms and distributed computing.</span></span></p>
<p><span style="font-size: small"><span style="color: #000000">By 2004 / 2005, pyrosequencing had been brought to commercial viability by 454 Life Sciences. This new sequencing methods generated reads much shorter than from Sanger sequencing: initially about 100 bases, now 400 bases and expected to grow to 1000 bases by the end of 2010. However, due to the much higher throughput and lower cost than Sanger sequencing, the adoption of this technology by genome centers pushed development of sequence assemblers to deal with this new type of sequences. The sheer amount of data coupled with technology specific error patterns in the reads delayed development of assemblers, at the beginning in 2004 only the Newbler assembler from 454 was available. Presented in mid 2007<sup id="cite_ref-3" class="reference">[4]</sup>, the hybrid version of the MIRA assembler by Chevreux et al. was the first freely available assembler who could assemble 454 reads and mixtures of 454 reads and Sanger reads; using sequences from different sequencing technologies was subsequently coined <i>hybrid assembly</i>.</span></span></p>
<p><span style="font-size: small"><span style="color: #000000">Ironically, technological development of sequencing continued to improve in the wrong way (from a sequence assembly point of view). Since 2006, the Solexa technology is available and heavily used to generate roundabout 100 million reads per day on a single sequencing machine. Compare this to the 35 million reads of the human genome project which needed several years to be produced on hundreds of sequencing machines. The downside is that these reads have a length of only 36 bases (expected to grow to 50 bases by the end of 2008). This makes sequence alignment an even more daunting task. Presented by the end of 2007, the SHARCGS assembler<sup id="cite_ref-4" class="reference">[5]</sup> by Dohm et al. was the first published assembler that was used for an assembly with Solexa reads, quickly followed by a number of others.</span></span></p>
<h2><span style="font-size: small"><span style="color: #000000"><span id="Greedy_algorithm" class="mw-headline">Greedy algorithm</span></span></span></h2>
<p><span style="font-size: small"><span style="color: #000000">Given a set of sequence fragments the object is to find the Shortest common supersequence.</span></span></p>
<ol>
    <li><span style="font-size: small"><span style="color: #000000">calculate pairwise alignments of all fragments</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">choose two fragments with the largest overlap</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">merge chosen fragments</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">repeat step 2. and 3. until only one fragment is left</span> </span></li>
</ol>
<p><span style="font-size: small"><span style="color: #000000">The result is a suboptimal solution to the problem.</span></span></p>
<h2><span style="font-size: small"><span style="color: #000000"><span id="Available_assemblers" class="mw-headline">Available assemblers</span></span></span></h2>
<p><span style="font-size: small"><span style="color: #000000">The following table lists assemblers that have a de-novo assembly capability on at least one of the supported technologies.<sup id="cite_ref-5" class="reference">[6]</sup></span></span></p>
<p>
<table class="wikitable" border="1">
    <tbody>
        <tr>
            <th><span style="font-size: small"><span style="color: #000000">Name</span></span></th>
            <th><span style="font-size: small"><span style="color: #000000">Type</span></span></th>
            <th><span style="font-size: small"><span style="color: #000000">Technologies</span></span></th>
            <th><span style="font-size: small"><span style="color: #000000">Author</span></span></th>
            <th><span style="font-size: small"><span style="color: #000000">Presented / </span></span>
            <p><span style="font-size: small"><span style="color: #000000">Last updated</span></span></p>
            </th>
            <th><span style="font-size: small"><span style="color: #000000">Licence*</span></span></th>
            <th><span style="font-size: small"><span style="color: #000000">Homepage</span></span></th>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">ABySS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Solexa, SOLiD</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Simpson, J. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2008 / 2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">AMOS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Salzberg, S. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2002? / 2008?</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Celera WGA Assembler / CABOG</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(large) genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454, Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Myers, G. et al.; Miller G. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2004 / 2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">CLC Genomics Workbench</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454, Solexa, SOLiD</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">CLC bio</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2008 / 2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">C</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Edena</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">D. Hernandez, P. Fran&ccedil;ois, L. Farinelli, M. Osteras, and J. Schrenzel.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2008</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">C</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Euler</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454 (,Solexa&nbsp;?)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Pevzner, P. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2001 / 2006?</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(C / NC-A?)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Euler-sr</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">454, Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Chaisson, MJ. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2008</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">NC-A</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Forge</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(large) genomes, EST, metagenomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">454, Solexa , SOLID, Sanger</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Platt, DM, Evers, D.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Geneious</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454, Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Biomatters Ltd</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2009 / 2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">C</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">IDBA (Iterative De Bruijn graph short read Assembler)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(large) genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Yu Peng, Henry C. M. Leung, Siu-Ming Yiu, Francis Y. L. Chin</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(C / NC-A?)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">MIRA (Mimicking Intelligent Read Assembly)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes, ESTs</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454, Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Chevreux, B.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">1998 / 2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">NextGENe</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(small genomes?)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">454, Solexa, SOLiD</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Softgenetics</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2008</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">C</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Newbler</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes, ESTs</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">454, Sanger</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">454/Roche</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2009</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">C</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Phrap</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Green, P.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2002 / 2003 / 2008</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">C / NC-A</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">TIGR Assembler</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomic</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">-</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">1995 / 2003</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Ray<sup id="cite_ref-6" class="reference">[7]</sup></span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Illumina, mix of Illumina and 454, paired or not</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">S&eacute;bastien Boisvert, Fran&ccedil;ois Laviolette &amp; Jacques Corbeil.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS [GNU General Public License]</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Sequencher</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(small) genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Gene Codes Corporation</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">1991 / 2009</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">C</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">SeqMan NGen</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(small) genomes, ESTs</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454, Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">DNASTAR</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">&nbsp;? / 2008</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">C</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">SHARCGS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(small) genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Dohm et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2007 / 2007</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">SOPRA</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Solexa, SOLiD, Sanger, 454</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Dayarian, A. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2010 / 2010</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">SSAKE</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(small) genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Solexa (SOLiD? Helicos?)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Warren, R. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2007 / 2007</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">SOAPdenovo</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Li, R. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2009 / 2009</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Closed</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Staden gap4 package</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">BACs (, small genomes?)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Staden et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">1991 / 2008</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">VCAKE</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(small) genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Solexa (SOLiD?, Helicos?)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Jeck, W. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2007 / 2007</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Phusion assembler</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(large) genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Mullikin JC, et.al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2003</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Quality Value Guided SRA (QSRA)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, Solexa</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Bryant DW, et.al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2009</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td><span style="font-size: small"><span style="color: #000000">Velvet (algorithm)</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">(small) genomes</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Sanger, 454, Solexa, SOLiD</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">Zerbino, D. et al.</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">2007 / 2009</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">OS</span></span></td>
            <td><span style="font-size: small"><span style="color: #000000">link</span></span></td>
        </tr>
        <tr>
            <td style="border-top: #333 1px solid" colspan="7"><span style="font-size: small"><span style="color: #000000"><small>*<b>Licences:</b> OS = Open Source; C = Commercial; C / NC-A = Commercial but free for non-commercial and academics; Brackets = unclear, but most likely C / NC-A</small></span></span></td>
        </tr>
    </tbody>
</table>
</p>
<h2><span style="font-size: large"><span style="color: #000000"><span id="See_also" class="mw-headline">See also</span></span></span></h2>
<ul>
    <li><span style="font-size: small"><span style="color: #000000">[[Sequence alignment]]</span> </span></li>
    <li><span style="font-size: small"><span style="color: #000000">Genome assembly</span> </span></li>
</ul>
<h2><span style="font-size: large"><span id="References" class="mw-headline">References</span></span></h2>
<ol class="references">
    <li id="cite_note-0"><span style="font-size: small"><b><a href="#cite_ref-0"><font color="#0645ad">^</font></a></b></span><span style="font-size: small"> <span class="citation Journal">Myers EW, Sutton GG, Delcher AL, <i>et al.</i> (March 2000). </span></span><span class="citation Journal"><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.sciencemag.org/cgi/pmidlookup?view=long&amp;pmid=10731133"><font color="#3366bb">&quot;A whole-genome assembly of Drosophila&quot;</font></a></span><span style="font-size: small">. <i>Science</i> <b>287</b> (5461): 2196&ndash;204. </span><span style="font-size: small"><a class="mw-redirect" title="PubMed Identifier" href="/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a></span><span style="font-size: small">&nbsp;</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/10731133"><font color="#3366bb">10731133</font></a></span><span style="font-size: small"><span class="printonly">. </span></span></span><span style="font-size: large"><span class="citation Journal"><span class="printonly"><a class="external free" rel="nofollow" href="http://www.sciencemag.org/cgi/pmidlookup?view=long&amp;pmid=10731133"><span style="font-size: small"><font color="#3366bb">http://www.sciencemag.org/cgi/pmidlookup?view=long&amp;pmid=10731133</font></span></a></span></span></span><span style="font-size: small"><span class="citation Journal">.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=A+whole-genome+assembly+of+Drosophila&amp;rft.jtitle=Science&amp;rft.aulast=Myers+EW%2C+Sutton+GG%2C+Delcher+AL%2C+%27%27et+al.%27%27&amp;rft.au=Myers+EW%2C+Sutton+GG%2C+Delcher+AL%2C+%27%27et+al.%27%27&amp;rft.date=March+2000&amp;rft.volume=287&amp;rft.issue=5461&amp;rft.pages=2196%E2%80%93204&amp;rft_id=info:pmid/10731133&amp;rft_id=http%3A%2F%2Fwww.sciencemag.org%2Fcgi%2Fpmidlookup%3Fview%3Dlong%26pmid%3D10731133&amp;rfr_id=info:sid/en.wikipedia.org:Sequence_assembly"><span style="display: none">&nbsp;</span></span> </span></li>
    <li id="cite_note-1"><span style="font-size: small"><b><a href="#cite_ref-1"><font color="#0645ad">^</font></a></b></span><span style="font-size: small"> <span class="citation Journal">Batzoglou S, Jaffe DB, Stanley K, <i>et al.</i> (January 2002). </span></span><span class="citation Journal"><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.genome.org/cgi/pmidlookup?view=long&amp;pmid=11779843"><font color="#3366bb">&quot;ARACHNE: a whole-genome shotgun assembler&quot;</font></a></span><span style="font-size: small">. <i>Genome Res.</i> <b>12</b> (1): 177&ndash;89. </span><span style="font-size: small"><a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0645ad">doi</font></a></span><span style="font-size: small">:</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://dx.doi.org/10.1101%2Fgr.208902"><font color="#3366bb">10.1101/gr.208902</font></a></span><span style="font-size: small">. </span><span style="font-size: small"><a class="mw-redirect" title="PubMed Identifier" href="/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a></span><span style="font-size: small">&nbsp;</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/11779843"><font color="#3366bb">11779843</font></a></span><span style="font-size: small">. </span><span style="font-size: small"><a title="PubMed Central" href="/wiki/PubMed_Central"><font color="#0645ad">PMC</font></a></span><span style="font-size: small">&nbsp;</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=155255"><font color="#3366bb">155255</font></a></span><span style="font-size: small"><span class="printonly">. </span></span></span><span style="font-size: large"><span class="citation Journal"><span class="printonly"><a class="external free" rel="nofollow" href="http://www.genome.org/cgi/pmidlookup?view=long&amp;pmid=11779843"><span style="font-size: small"><font color="#3366bb">http://www.genome.org/cgi/pmidlookup?view=long&amp;pmid=11779843</font></span></a></span></span></span><span style="font-size: small"><span class="citation Journal">.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=ARACHNE%3A+a+whole-genome+shotgun+assembler&amp;rft.jtitle=Genome+Res.&amp;rft.aulast=Batzoglou+S%2C+Jaffe+DB%2C+Stanley+K%2C+%27%27et+al.%27%27&amp;rft.au=Batzoglou+S%2C+Jaffe+DB%2C+Stanley+K%2C+%27%27et+al.%27%27&amp;rft.date=January+2002&amp;rft.volume=12&amp;rft.issue=1&amp;rft.pages=177%E2%80%9389&amp;rft_id=info:doi/10.1101%2Fgr.208902&amp;rft_id=info:pmid/11779843&amp;rft_id=http%3A%2F%2Fwww.genome.org%2Fcgi%2Fpmidlookup%3Fview%3Dlong%26pmid%3D11779843&amp;rfr_id=info:sid/en.wikipedia.org:Sequence_assembly"><span style="display: none">&nbsp;</span></span> </span></li>
    <li id="cite_note-2"><span style="font-size: small"><b><a href="#cite_ref-2"><font color="#0645ad">^</font></a></b></span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://amos.sourceforge.net/"><font color="#3366bb">AMOS page</font></a></span><span style="font-size: small"> with links to various papers </span></li>
    <li id="cite_note-3"><span style="font-size: small"><b><a href="#cite_ref-3"><font color="#0645ad">^</font></a></b></span><span style="font-size: small"> Copy in Google groups of the </span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://groups.google.com/group/bionet.software/browse_thread/thread/b34b348011d04f0e?fwc=1"><font color="#3366bb">post announcing MIRA 2.9.8 hybrid version</font></a></span><span style="font-size: small"> in the bionet.software Usenet group </span></li>
    <li id="cite_note-4"><span style="font-size: small"><b><a href="#cite_ref-4"><font color="#0645ad">^</font></a></b></span><span style="font-size: small"> <span class="citation Journal">Dohm JC, Lottaz C, Borodina T, Himmelbauer H (November 2007). </span></span><span class="citation Journal"><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.genome.org/cgi/pmidlookup?view=long&amp;pmid=17908823"><font color="#3366bb">&quot;SHARCGS, a fast and highly accurate short-read assembly algorithm for de novo genomic sequencing&quot;</font></a></span><span style="font-size: small">. <i>Genome Res.</i> <b>17</b> (11): 1697&ndash;706. </span><span style="font-size: small"><a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0645ad">doi</font></a></span><span style="font-size: small">:</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://dx.doi.org/10.1101%2Fgr.6435207"><font color="#3366bb">10.1101/gr.6435207</font></a></span><span style="font-size: small">. </span><span style="font-size: small"><a class="mw-redirect" title="PubMed Identifier" href="/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a></span><span style="font-size: small">&nbsp;</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/17908823"><font color="#3366bb">17908823</font></a></span><span style="font-size: small">. </span><span style="font-size: small"><a title="PubMed Central" href="/wiki/PubMed_Central"><font color="#0645ad">PMC</font></a></span><span style="font-size: small">&nbsp;</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=2045152"><font color="#3366bb">2045152</font></a></span><span style="font-size: small"><span class="printonly">. </span></span></span><span style="font-size: large"><span class="citation Journal"><span class="printonly"><a class="external free" rel="nofollow" href="http://www.genome.org/cgi/pmidlookup?view=long&amp;pmid=17908823"><span style="font-size: small"><font color="#3366bb">http://www.genome.org/cgi/pmidlookup?view=long&amp;pmid=17908823</font></span></a></span></span></span><span style="font-size: small"><span class="citation Journal">.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=SHARCGS%2C+a+fast+and+highly+accurate+short-read+assembly+algorithm+for+de+novo+genomic+sequencing&amp;rft.jtitle=Genome+Res.&amp;rft.aulast=Dohm+JC%2C+Lottaz+C%2C+Borodina+T%2C+Himmelbauer+H&amp;rft.au=Dohm+JC%2C+Lottaz+C%2C+Borodina+T%2C+Himmelbauer+H&amp;rft.date=November+2007&amp;rft.volume=17&amp;rft.issue=11&amp;rft.pages=1697%E2%80%93706&amp;rft_id=info:doi/10.1101%2Fgr.6435207&amp;rft_id=info:pmid/17908823&amp;rft_id=http%3A%2F%2Fwww.genome.org%2Fcgi%2Fpmidlookup%3Fview%3Dlong%26pmid%3D17908823&amp;rfr_id=info:sid/en.wikipedia.org:Sequence_assembly"><span style="display: none">&nbsp;</span></span> </span></li>
    <li id="cite_note-5"><span style="font-size: small"><b><a href="#cite_ref-5"><font color="#0645ad">^</font></a></b></span><span style="font-size: medium"><a class="external text" rel="nofollow" href="http://seqanswers.com/forums/showthread.php?t=43"><span style="font-size: small"><font color="#3366bb">list of software including mapping assemblers in the SeqAnswers discussion forum.</font></span></a></span></li>
    <li id="cite_note-6"><span style="font-size: small"><b><a href="#cite_ref-6"><font color="#0645ad">^</font></a></b></span><span style="font-size: small"> <span class="citation Journal">Boisvert S, Laviolette F, Corbeil J. (October 2010). </span></span><span class="citation Journal"><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.liebertonline.com/doi/abs/10.1089/cmb.2009.0238"><font color="#3366bb">&quot;Ray: simultaneous assembly of reads from a mix of high-throughput sequencing technologies.&quot;</font></a></span><span style="font-size: small">. <i>J Comput Biol.</i> <b>17</b> (11): 1519-33. </span><span style="font-size: small"><a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0645ad">doi</font></a></span><span style="font-size: small">:</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://dx.doi.org/10.1089%2Fcmb.2009.0238"><font color="#3366bb">10.1089/cmb.2009.0238</font></a></span><span style="font-size: small">. </span><span style="font-size: small"><a class="mw-redirect" title="PubMed Identifier" href="/wiki/PubMed_Identifier"><font color="#0645ad">PMID</font></a></span><span style="font-size: small">&nbsp;</span><span style="font-size: small"><a class="external text" rel="nofollow" href="http://www.ncbi.nlm.nih.gov/pubmed/20958248"><font color="#3366bb">20958248</font></a></span><span style="font-size: small"><span class="printonly">. </span></span></span><span style="font-size: large"><span class="citation Journal"><span class="printonly"><a class="external free" rel="nofollow" href="http://www.liebertonline.com/doi/abs/10.1089/cmb.2009.0238"><span style="font-size: small"><font color="#3366bb">http://www.liebertonline.com/doi/abs/10.1089/cmb.2009.0238</font></span></a></span></span></span><span style="font-size: small"><span class="citation Journal">.</span> </span></li>
</ol>